Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder

Lily C. Wang, Evanguelos Xylinas, Matthew T. Kent, Luis A. Kluth, Michael Rink, Asha Jamzadeh, Malte Rieken, Bashir Al Hussein Al Awamlh, Quoc Dien Trinh, Maxine Sun, Pierre I. Karakiewicz, Giacomo Novara, James Chrystal, Marc Zerbib, Douglas S. Scherr, Yair Lotan, Andrew Vickers, Shahrokh F. Shariat

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objectives: Tissue-based markers improve the accuracy of prediction models in urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative exposure also affect outcomes. To evaluate whether the combination of molecular markers and smoking features further improved the prognostication of patients who underwent radical cystectomy (RC) for UCB. Materials and methods: A total of 588 patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005. Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on tissue microarrays from the RC specimen. Smoking features were routinely assessed at diagnosis. Multivariable Cox regression models assessed time to disease recurrence and cancer-specific mortality. Results: Of the 588 patients, 128 were never (22%), 283 former (48%), and 177 current smokers (30%). In total, 227 patients experienced disease recurrence, whereas 190 died of UCB. Smoking status was independently associated with both outcomes (hazard ratio [HR] = 1.48 and 2.62, for former and current vs. never smokers, respectively, P<0.001). All markers were significantly associated with both outcomes (P<0.05) except for survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27 increased the discrimination of clinicopathologic model for former and current vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c-indices of 0.741 and 0.740 for former and current vs. never smokers, respectively). The further addition of smoking features and biomarker status improved the discrimination of the model (c-indices of 0.783 and 0.786 for former and current vs. never smokers, respectively). Conclusions: We confirmed that smoking information and tissue markers status improve prognostication of UCB outcomes after RC; the combination of both reaching the highest level of discrimination.

Original languageEnglish (US)
Pages (from-to)433-440
Number of pages8
JournalUrologic Oncology: Seminars and Original Investigations
Volume32
Issue number4
DOIs
StatePublished - 2014

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Urinary Bladder
Cystectomy
Smoking
Carcinoma
Recurrence
Lymph Node Excision
Proportional Hazards Models
Cell Cycle
Biomarkers
Immunohistochemistry
Mortality
Neoplasms

Keywords

  • Biomarkers
  • Prognostic
  • Radical cystectomy
  • Smoking
  • Survival
  • Urothelial carcinoma of the bladder

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder. / Wang, Lily C.; Xylinas, Evanguelos; Kent, Matthew T.; Kluth, Luis A.; Rink, Michael; Jamzadeh, Asha; Rieken, Malte; Al Awamlh, Bashir Al Hussein; Trinh, Quoc Dien; Sun, Maxine; Karakiewicz, Pierre I.; Novara, Giacomo; Chrystal, James; Zerbib, Marc; Scherr, Douglas S.; Lotan, Yair; Vickers, Andrew; Shariat, Shahrokh F.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 32, No. 4, 2014, p. 433-440.

Research output: Contribution to journalArticle

Wang, LC, Xylinas, E, Kent, MT, Kluth, LA, Rink, M, Jamzadeh, A, Rieken, M, Al Awamlh, BAH, Trinh, QD, Sun, M, Karakiewicz, PI, Novara, G, Chrystal, J, Zerbib, M, Scherr, DS, Lotan, Y, Vickers, A & Shariat, SF 2014, 'Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder', Urologic Oncology: Seminars and Original Investigations, vol. 32, no. 4, pp. 433-440. https://doi.org/10.1016/j.urolonc.2013.10.015
Wang, Lily C. ; Xylinas, Evanguelos ; Kent, Matthew T. ; Kluth, Luis A. ; Rink, Michael ; Jamzadeh, Asha ; Rieken, Malte ; Al Awamlh, Bashir Al Hussein ; Trinh, Quoc Dien ; Sun, Maxine ; Karakiewicz, Pierre I. ; Novara, Giacomo ; Chrystal, James ; Zerbib, Marc ; Scherr, Douglas S. ; Lotan, Yair ; Vickers, Andrew ; Shariat, Shahrokh F. / Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder. In: Urologic Oncology: Seminars and Original Investigations. 2014 ; Vol. 32, No. 4. pp. 433-440.
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abstract = "Objectives: Tissue-based markers improve the accuracy of prediction models in urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative exposure also affect outcomes. To evaluate whether the combination of molecular markers and smoking features further improved the prognostication of patients who underwent radical cystectomy (RC) for UCB. Materials and methods: A total of 588 patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005. Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on tissue microarrays from the RC specimen. Smoking features were routinely assessed at diagnosis. Multivariable Cox regression models assessed time to disease recurrence and cancer-specific mortality. Results: Of the 588 patients, 128 were never (22{\%}), 283 former (48{\%}), and 177 current smokers (30{\%}). In total, 227 patients experienced disease recurrence, whereas 190 died of UCB. Smoking status was independently associated with both outcomes (hazard ratio [HR] = 1.48 and 2.62, for former and current vs. never smokers, respectively, P<0.001). All markers were significantly associated with both outcomes (P<0.05) except for survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27 increased the discrimination of clinicopathologic model for former and current vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c-indices of 0.741 and 0.740 for former and current vs. never smokers, respectively). The further addition of smoking features and biomarker status improved the discrimination of the model (c-indices of 0.783 and 0.786 for former and current vs. never smokers, respectively). Conclusions: We confirmed that smoking information and tissue markers status improve prognostication of UCB outcomes after RC; the combination of both reaching the highest level of discrimination.",
keywords = "Biomarkers, Prognostic, Radical cystectomy, Smoking, Survival, Urothelial carcinoma of the bladder",
author = "Wang, {Lily C.} and Evanguelos Xylinas and Kent, {Matthew T.} and Kluth, {Luis A.} and Michael Rink and Asha Jamzadeh and Malte Rieken and {Al Awamlh}, {Bashir Al Hussein} and Trinh, {Quoc Dien} and Maxine Sun and Karakiewicz, {Pierre I.} and Giacomo Novara and James Chrystal and Marc Zerbib and Scherr, {Douglas S.} and Yair Lotan and Andrew Vickers and Shariat, {Shahrokh F.}",
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T1 - Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder

AU - Wang, Lily C.

AU - Xylinas, Evanguelos

AU - Kent, Matthew T.

AU - Kluth, Luis A.

AU - Rink, Michael

AU - Jamzadeh, Asha

AU - Rieken, Malte

AU - Al Awamlh, Bashir Al Hussein

AU - Trinh, Quoc Dien

AU - Sun, Maxine

AU - Karakiewicz, Pierre I.

AU - Novara, Giacomo

AU - Chrystal, James

AU - Zerbib, Marc

AU - Scherr, Douglas S.

AU - Lotan, Yair

AU - Vickers, Andrew

AU - Shariat, Shahrokh F.

PY - 2014

Y1 - 2014

N2 - Objectives: Tissue-based markers improve the accuracy of prediction models in urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative exposure also affect outcomes. To evaluate whether the combination of molecular markers and smoking features further improved the prognostication of patients who underwent radical cystectomy (RC) for UCB. Materials and methods: A total of 588 patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005. Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on tissue microarrays from the RC specimen. Smoking features were routinely assessed at diagnosis. Multivariable Cox regression models assessed time to disease recurrence and cancer-specific mortality. Results: Of the 588 patients, 128 were never (22%), 283 former (48%), and 177 current smokers (30%). In total, 227 patients experienced disease recurrence, whereas 190 died of UCB. Smoking status was independently associated with both outcomes (hazard ratio [HR] = 1.48 and 2.62, for former and current vs. never smokers, respectively, P<0.001). All markers were significantly associated with both outcomes (P<0.05) except for survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27 increased the discrimination of clinicopathologic model for former and current vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c-indices of 0.741 and 0.740 for former and current vs. never smokers, respectively). The further addition of smoking features and biomarker status improved the discrimination of the model (c-indices of 0.783 and 0.786 for former and current vs. never smokers, respectively). Conclusions: We confirmed that smoking information and tissue markers status improve prognostication of UCB outcomes after RC; the combination of both reaching the highest level of discrimination.

AB - Objectives: Tissue-based markers improve the accuracy of prediction models in urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative exposure also affect outcomes. To evaluate whether the combination of molecular markers and smoking features further improved the prognostication of patients who underwent radical cystectomy (RC) for UCB. Materials and methods: A total of 588 patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005. Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on tissue microarrays from the RC specimen. Smoking features were routinely assessed at diagnosis. Multivariable Cox regression models assessed time to disease recurrence and cancer-specific mortality. Results: Of the 588 patients, 128 were never (22%), 283 former (48%), and 177 current smokers (30%). In total, 227 patients experienced disease recurrence, whereas 190 died of UCB. Smoking status was independently associated with both outcomes (hazard ratio [HR] = 1.48 and 2.62, for former and current vs. never smokers, respectively, P<0.001). All markers were significantly associated with both outcomes (P<0.05) except for survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27 increased the discrimination of clinicopathologic model for former and current vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c-indices of 0.741 and 0.740 for former and current vs. never smokers, respectively). The further addition of smoking features and biomarker status improved the discrimination of the model (c-indices of 0.783 and 0.786 for former and current vs. never smokers, respectively). Conclusions: We confirmed that smoking information and tissue markers status improve prognostication of UCB outcomes after RC; the combination of both reaching the highest level of discrimination.

KW - Biomarkers

KW - Prognostic

KW - Radical cystectomy

KW - Smoking

KW - Survival

KW - Urothelial carcinoma of the bladder

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